A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

AstraZeneca

Status and phase

Enrolling

Phase 1

Conditions

Myeloid Neoplasms (AML/MDS)

Other Solid Tumors

Colorectal Carcinoma

Breast Cancer

Pancreatic Adenocarcinoma

Non-small Cell Lung Cancer

Ovarian Cancer

Head and Neck Squamous Cell Carcinoma

Treatments

Biological: NT-175

Study type

Interventional

Funder types

Industry

Identifiers

NCT05877599

NT-175-201

D8690C00001 (Other Identifier)

Details and patient eligibility

About

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies

Full description

This is a Phase 1, open-label, multicentre platform study to evaluate the safety and preliminary antitumour activity of NT-175 in HLA-A*02:01 participants with advanced malignancies that are positive for the TP53 R175H mutation.

Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D.

Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at or below the MTD in disease specific histologies and determine the RP2D.

Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of NT-175 at the RP2D in disease specific settings.

Enrollment

45 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria (Module 1)

Subjects must be at least 18 years of age
Subject must be diagnosed with one of the histologies below:
- NSCLC
- Colorectal adenocarcinoma
- HNSCC
- Pancreatic adenocarcinoma
- Breast cancer
- Ovarian cancer
- Any other solid tumor
Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A*02:01 positive (at least 1 allele)
Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
Subject has at least 1 measurable lesion
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Adequate hematological, renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria (Module 1)

Any another primary malignancy within the 3 years prior to enrollment
Known, active primary central nervous system (CNS) malignancy
History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
Any form of primary immunodeficiency.
Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Key Inclusion Criteria (Module 2 - hematological malignancies)

At least 18 years of age
Diagnosis of AML or MDS that allows for efficacy assessments
Confirmation of TP53 R175H variant mutation in cancer cells
Subject must be HLA-A*02:01 positive (at least 1 allele)
ECOG performance status of 0 to 1

Key Exclusion Criteria (Module 2 - hematological malignancy)

Acute promyelocytic leukaemia or isolated extramedullary disease
Another primary malignancy within 2 years (with exceptions)
HSCT within 100 days or immunosuppression for GvHD within 4 weeks
History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells
Prior stroke, ischemic attack, significant cardiac disease, heart failure
Prior adoptive modified cell therapy
Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.